Hyaluronan oligomers sensitize chronic myeloid leukemia cell lines to the effect of Imatinib.

LOMPARDÍA, SL; DÍAZ, M; PAPADEMETRIO, DL; MASCARÓ, M; PIBUEL, M; ÁLVAREZ, E; HAJOS, SE

GLYCOBIOLOGY

OXFORD UNIV PRESS INC

Año: 2015

0959-6658

Glycobiology. 2016Apr;26(4):343-52. doi: 10.1093/glycob/cwv107. Epub 2015 Nov 17.Hyaluronan oligomerssensitize chronic myeloid leukemia cell lines to the effect of Imatinib.Lompardía SL, Díaz M, PapademetrioDL, Mascaró M, Pibuel M, Álvarez E, Hajos SE Chronic myeloid leukemia is a myeloproliferativesyndrome characterized by the presence of the Philadelphia chromosome (Ph),generated by a reciprocal translocation occurring between chromosomes 9 and 22[t(9;22)(q34;q11)]. As a consequence, a fusion gene (bcr-abl) encoding aconstitutively active kinase is generated. The first-line treatment consists onBCR-ABL inhibitors such as Imatinib, Nilotinib and Dasatinib. Nevertheless,such treatment may lead to the selection of resistant cells. Therefore, findingmolecules that enhance the anti-proliferative effect of first-line drugs is ofvalue. Hyaluronan oligomers (oHA) are known to be able to sensitize severaltumor cells to chemotherapy. We have previously demonstrated that oHA can revertVincristine resistance in mouse lymphoma and human leukemia cell lines.However, little is known about the role of oHA in hematological malignancies.The aim of this work was to determine whether oHA are able to modulate theanti-proliferative effect of Imatinib in chronic myeloid leukemia (CML) celllines. The effect on apoptosis and senescence as well as the involvement ofsignaling pathways were also evaluated. For this purpose, the human CML celllines K562 and Kv562 (resistant) were used. We demonstrated that oHA sensitizedboth cell lines to the anti-proliferative effect of Imatinib increasingapoptosis and senescence. Moreover, this effect would be accomplished throughthe down-regulation of the PI3K signaling pathway. These findings highlight thepotential of oHA when used as a co-adjuvant therapy for chronic myeloidleukemia.